GNPS - Bile Acid Standards for MSV000093200
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Pieter C Dorrestein
PROVIDER: MSV000093262 | GNPS | Thu Nov 02 10:20:00 GMT 2023
REPOSITORIES: GNPS
Similar Datasets
Project description:Bile acid standards run alongside MSV000093200 (Gates Foundation SEPSIS project).
2023-11-02 | MSV000093262 | MassIVE
Project description:Bile acid standards were run alongside mouse diet samples to annotate bile acids as Level 1 annotations.
2023-02-22 | MSV000091347 | MassIVE
Project description:Bile acid therapeutics for NASH
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Project description:MS/MS fragmentation data on bile acid standards were acquired on the QE - with a gradient developed to separate between isomeric pairs on a Polar C18 column and a fragmentation energy of NCE 45.
2023-05-22 | MSV000092003 | MassIVE
Project description:Background & Aims: Wilson disease (WD) is an autosomal recessive disorder that results in excessive hepatic copper causing hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver failure. Previous studies have revealed dysregulation of many FXR metabolic target genes in animal models of WD, including Bsep, the major determinant of bile flow. Approach & Results: We tested the hypothesis that the FXR-cistrome is decreased in Atp7b-/- mice in accord with dysregulated bile acid homeostasis. RNA-Seq and ChIP-Seq analyses of Atp7b-/- and wild-type (WT) mouse livers confirmed that significantly altered transcripts and FXR-binding events overlapped. Decreased FXR occupancy in Atp7b-/- versus WT mice was observed genes of metabolic pathways and bile acid homeostasis, while enrichment of FXR binding was observed pathways associated with cellular damage, such as the focal adhesion pathway. Consistent with decreased FXR function, serum and liver bile acid concentrations were higher in Atp7b-/- mice than in WT mice. Comparison of bile acid profiles in the serum of WD patients with “liver,” “neurological,” or “mixed” disease vs. healthy controls also revealed increases in specific bile acids in WD-liver vs. healthy controls. Conclusions: Atp7b-/- mice and WD patients exhibited changes in serum bile acid speciation, likely due to FXR dysfunction. These findings provide new insights into possible aberrant bile acid homeostasis in patients with WD.
2025-06-04 | GSE287020 | GEO
Project description:Specific bile acids are potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis, and the microbiota. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis (Cyp7a1, Cyp8b1) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway and modifies the biliary bile acid composition. In contrast, loss-of-function studies using MafG(+/-) mice causes de-repression of the same genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR.
2016-02-04 | GSE77529 | GEO
Project description:Background & Aims: Wilson disease (WD) is an autosomal recessive disorder that results in excessive hepatic copper causing hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver failure. Previous studies have revealed dysregulation of many FXR metabolic target genes in animal models of WD, including Bsep, the major determinant of bile flow. Approach & Results: We tested the hypothesis that the FXR-cistrome is decreased in Atp7b-/- mice in accord with dysregulated bile acid homeostasis. RNA-Seq and ChIP-Seq analyses of Atp7b-/- and wild-type (WT) mouse livers confirmed that significantly altered transcripts and FXR-binding events overlapped. Decreased FXR occupancy in Atp7b-/- versus WT mice was observed genes of metabolic pathways and bile acid homeostasis, while enrichment of FXR binding was observed pathways associated with cellular damage, such as the focal adhesion pathway. Consistent with decreased FXR function, serum and liver bile acid concentrations were higher in Atp7b-/- mice than in WT mice. Comparison of bile acid profiles in the serum of WD patients with “liver,” “neurological,” or “mixed” disease vs. healthy controls also revealed increases in specific bile acids in WD-liver vs. healthy controls. Conclusions: Atp7b-/- mice and WD patients exhibited changes in serum bile acid speciation, likely due to FXR dysfunction. These findings provide new insights into possible aberrant bile acid homeostasis in patients with WD.
2025-06-04 | GSE286956 | GEO
Project description:Summary Ex vivo liver normothermic machine perfusion (NMP) does not fully recapitulate physiological liver function due to the absence of the enterohepatic circulation as only infusion of the bile acid taurocholate (TCA) is applied in most protocols. In this study we characterized the de novo bile acid synthesis and cholesterol homeostasis during liver NMP. We hypothesized that addition of a more diverse pool of (conjugated)bile acids during liver NMP would decrease the metabolic burden of de novo synthesis and thereby improve liver function during NMP. Method First, human and porcine livers were perfused for 360 min at 37°C and perfusate containing TCA (gene expression at t=0min and t=360min was measured by RNAseq). Next, the infusion of different conjugated bile acid mixes was assessed during porcine and human liver perfusion. Perfusate, bile and tissue samples were obtained to study liver viability, functionality, gene expression (qPCR), cholesterol and bile acid levels. Result During human and porcine perfusions with TCA infusion, composition of bile was comparable to literature however, synthesis rates were above physiological average and a decrease over time in cholesterol perfusate levels was observed. Additionally, over time a decreased expression of bile acid synthesis related genes, increased gene expression of cholesterol metabolism related genes and decreased expression in bile acid-dependent uptake and efflux transporters were detected (RNAseq). Upon infusion of a conjugated bile acid mix lower AST and ALT values and stable cholesterol homeostasis was] observed after 720 min of perfusion. Perfused human livers showed appropriate function and good functioning livers showed rapid bile acid clearance from the perfusate into the bile. Conclusion This study reveals new insights that infusion of (un)conjugated bile acids in NMP alleviated the burden of the de novo bile acid synthesis and improved liver function.
2025-10-14 | GSE279712 | GEO
Project description:Bile acids are multifunctional signaling molecules that play significant roles in maintaining microbial homeostasis. N6-methyladenine (m6A), the most abundant epitranscriptomic modification, mediates various biological processes by modulating RNA metabolism. However, the precise regulatory mechanisms of m6A methylation in bile acid metabolism, and its downstream effects on microbiota remain unclear. In this study, liver-specific Mettl14 knockout (Mettl14-LKO) reshaped bile acid profile and expression levels of protein related to bile acid metabolism, namely CYP7A1, FXR, and BSEP. M6A-seq data revealed m6A methylated peaks on CYP7A1. Mettl14-LKO significantly elevated expression of m6A “reader” IGF2BP3. Knockdown of IGF2BP3 inhibited CYP7A1 expression by decreasing mRNA stability. Mechanistically, Mettl14-LKO promoted bile acid synthesis by upregulating CYP7A1 expression in an m6A-IGF2BP3-dependent manner. Interestingly, Mettl14-LKO reduced bile acid content in ileum due to decreased BSEP level in liver. Noteworthy, we discovered for the first time that Mettl14 knockout in the liver altered fecal microbiota composition. Specifically, it changed the abundance of Cyanobacteria and Patescibacteria at phylum level, and Lachnochostridium, Candidatus-Saccharimonas, and Roseburia at genera level. Remarkably, Roseburia was negatively correlated with the bile acid levels and CYP7A1 expression. Our findings provide new insights into the role of METTL14 in regulating bile acid homeostasis and its impact on fecal microbiota. Roseburia emerges as a potential target for addressing metabolic diseases linked to disrupted METTL14 signaling.
2025-04-09 | GSE293836 | GEO